Threonine (symbol Thr or T) is an
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
that is used in the
biosynthesis of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s. It contains an
α-amino group (which is in the protonated −NH form under biological conditions), a
carboxyl group
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
(which is in the deprotonated −COO
− form under biological conditions), and a side chain containing a
hydroxyl group, making it a polar, uncharged amino acid. It is
essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Threonine is synthesized from
aspartate in bacteria such as
''E. coli''. It is
encoded
In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...
by all the
codons starting AC (ACU, ACC, ACA, and ACG).
Threonine sidechains are often hydrogen bonded; the most common small motifs formed are based on interactions with
serine:
ST turns,
ST motif The ST motif is a commonly occurring feature in proteins and polypeptides. It consists of four or five amino acid residues with either serine or threonine as the first residue (residue ''i''). It is defined by two internal hydrogen bonds. One is bet ...
s (often at the beginning of alpha helices) and
ST staple The ST staple is a common four- or five-amino acid residue motif in proteins and polypeptides with serine or threonine as the C-terminal residue. It is characterized by a single hydrogen bond between the hydroxyl group of the serine or threoni ...
s (usually at the middle of alpha helices).
Modifications
The threonine residue is susceptible to numerous
posttranslational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribo ...
s. The
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydro ...
side-chain can undergo
''O''-linked glycosylation. In addition, threonine residues undergo
phosphorylation through the action of a threonine
kinase. In its phosphorylated form, it can be referred to as
phosphothreonine
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO ...
. Phosphothreonine has three potential coordination sites (carboxyl, amine and phosphate group) and determination of the mode of coordination between phosphorylated ligands and metal ions occurring in an organism is important to explain the function of the phosphothreonine in biological processes.
History
Threonine was the last of the 20 common
proteinogenic
Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino aci ...
amino acids to be discovered. It was discovered in 1936 by
William Cumming Rose
William Cumming Rose (April 4, 1887 – September 25, 1985) was an American biochemist and nutritionist. He discovered the amino acid threonine, and his research determined the necessity for essential amino acids in diet and the minimum daily re ...
, collaborating with Curtis Meyer. The amino acid was named threonine because it was similar in structure to
threonic acid
Threonic acid is a sugar acid derived from threose. The -isomer is a metabolite of ascorbic acid (vitamin C). One study suggested that because -threonate inhibits DKK1 expression ''in vitro'', it may have potential in treatment of androgenic alope ...
, a four-carbon
monosaccharide with
molecular formula
In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...
C
4H
8O
5
Stereoisomers
Threonine is one of two proteinogenic amino acids with two
stereogenic
In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups cr ...
centers, the other being
isoleucine. Threonine can exist in four possible
stereoisomer
In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...
s with the following configurations: (2''S'',3''R''), (2''R'',3''S''), (2''S'',3''S'') and (2''R'',3''R''). However, the name
L-threonine is used for one single
stereoisomer
In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...
, (2''S'',3''R'')-2-amino-3-hydroxybutanoic acid. The second stereoisomer (2''S'',3''S''), which is rarely present in nature, is called
L-allothreonine. The two stereoisomers (2''R'',3''S'')- and (2''R'',3''R'')-2-amino-3-hydroxybutanoic acid are only of minor importance.
Biosynthesis
As an essential amino acid, threonine is not synthesized in humans, and needs to be present in proteins in the diet. Adult humans require about 20 mg/kg body weight/day.
In plants and microorganisms, threonine is synthesized from
aspartic acid via α-aspartyl-semialdehyde and
homoserine
Homoserine (also called isothreonine) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2OH. -Homoserine is not one of the common amino acids encoded by DNA. It differs from the proteinogenic amino acid serine by insertion of an additi ...
. Homoserine undergoes ''O''-phosphorylation; this phosphate
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
undergoes hydrolysis concomitant with relocation of the OH group. Enzymes involved in a typical biosynthesis of threonine include:
#
aspartokinase
Aspartate kinase or aspartokinase (AK) is an enzyme that catalyzes the phosphorylation of the amino acid aspartate. This reaction is the first step in the biosynthesis of three other amino acids: methionine, lysine, and threonine, known as the "a ...
#
β-aspartate semialdehyde dehydrogenase
#
homoserine dehydrogenase
In enzymology, a homoserine dehydrogenase () is an enzyme that catalyzes the chemical reaction
:L-homoserine + NAD(P)+ \rightleftharpoons L-aspartate 4-semialdehyde + NAD(P)H + H+
The 2 substrates of this enzyme are L-homoserine and NAD+ ...
#
homoserine kinase
In enzymology, a homoserine kinase () is an enzyme that catalyzes the chemical reaction
:ATP + L-homoserine \rightleftharpoons ADP + O-phospho-L-homoserine
Thus, the two substrates of this enzyme are ATP and L-homoserine, whereas its two pr ...
#
threonine synthase
The enzyme threonine synthase (EC 4.2.3.1) catalyzes the chemical reaction
:''O''-phospho-L-homoserine + H2O \rightleftharpoons L-threonine + phosphate
This enzyme belongs to the family of lyases, specifically those carbon-oxygen lyases acting ...
.
Metabolism
Threonine is metabolized in at least three ways:
* In many animals it is converted to
pyruvate via
threonine dehydrogenase
In enzymology, a L-threonine 3-dehydrogenase () is an enzyme that catalyzes the chemical reaction
:L-threonine + NAD+ \rightleftharpoons L-2-amino-3-oxobutanoate + NADH + H+
Thus, the two substrates of this enzyme are L-threonine and NAD+, ...
. An intermediate in this pathway can undergo
thiolysis Thiolysis is a reaction with a thiol (R-SH) that cleaves one compound into two. Thiolysis involves the addition of coenzyme A to one of the products. This reaction is similar to hydrolysis, which involves water instead of a thiol. This reaction is s ...
with CoA to produce
acetyl-CoA and
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
.
* In humans the gene for threonine dehydrogenase is an inactive
pseudogene, so threonine is converted to
α-ketobutyrate. The mechanism of the first step is analogous to that catalyzed by
serine dehydratase
Serine dehydratase or L-serine ammonia lyase (SDH) is in the β-family of pyridoxal phosphate-dependent (PLP) enzymes. SDH is found widely in nature, but its structural and properties vary among species. SDH is found in yeast, bacteria, and the ...
, and the serine and threonine dehydratase reactions are probably catalyzed by the same enzyme.
* In many organisms it is
O-phosphorylated by
a kinase preparatory to further metabolism. This is especially important in
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
as part of the
biosynthesis of cobalamin
Cobalamin biosynthesis is the process by which bacteria and archea make cobalamin, vitamin B12. Many steps are involved in converting aminolevulinic acid via uroporphyrinogen III and adenosylcobyric acid to the final forms in which it is used by ...
(
Vitamin B12
Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
), as the product is converted to
(R)-1-aminopropan-2-ol for incorporation into the vitamin's sidechain.
*Threonine is used to synthesize glycine during the endogenous production of L-carnitine in the brain and liver of rats.
Sources
Foods high in threonine include
cottage cheese
Cottage cheese is a curdled milk product with a mild flavor and a creamy, non-homogeneous, soupy texture. It is made from skimmed milk by draining the cheese, as opposed to pressing it to make cheese curd—retaining some of the whey and keep ...
,
poultry
Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, quails, ...
,
fish
Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of ...
,
meat,
lentil
The lentil (''Lens culinaris'' or ''Lens esculenta'') is an edible legume. It is an annual plant known for its lens-shaped seeds. It is about tall, and the seeds grow in pods, usually with two seeds in each. As a food crop, the largest pro ...
s,
black turtle bean and
sesame seeds.
Racemic
In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
threonine can be prepared from
crotonic acid
Crotonic acid ((2''E'')-but-2-enoic acid) is a short-chain unsaturated carboxylic acid, described by the formula CH3CH=CHCO2H. It is called crotonic acid because it was erroneously thought to be a saponification product of croton oil. It crysta ...
by alpha-functionalization using
mercury(II) acetate
Mercury(II) acetate is the chemical compound with the formula Hg( O2 CC H3)2. Commonly abbreviated Hg(OAc)2, this compound is employed as a reagent to generate organomercury compounds from unsaturated organic precursors. It is a white water-sol ...
.
[.]
References
External links
Threonine biosynthesisCID 205CID 6288
{{Glycinergics
Proteinogenic amino acids
Glucogenic amino acids
Ketogenic amino acids
Essential amino acids
Glycine receptor agonists